Monthly Archives: February 2009

REVIEW/ METANALYSIS: METFORMIN AND CANCER PREVENTION

This column last specifically reviewed the topic of metformin benefit on cancer reduction two months ago. We know that stress and bad diet -dysnutrition and lack of exercise – promote the   risks of fatigue, insulin resistance, lipidemia, diabetes, obesity, cancer, infection..

To put diabetes in perspective, we need to read the classic articles by

A J Hodgson of 1912 of his experience with diabetes over 20 years  in Canada, in which he posed as the “chief cause in the growing  epidemic of diabetes that past half century the rapid increase of intake of glucose or ‘corn syrup’, the astounding amounts being eaten at speed; and the nervous  stress and strain of American life”.  Nothing seems to have changed in the endless Western preference for exposure to stress and  lunatic  gluttony;  and  lunatic Regulatory  blindness the past century in doing nothing to enforce improvement in the food chain, while  cigarette smoking and cannabis have been drastically regulated. So much of what Hodgson wrote about the chief cause of epidemic ie type 2 diabetes remains true today- personal hygiene, the unwillingness to eat and exercise  sensibly;

 and by

Banting  Macleod  Best & Collip (  Toronto 1921) on the first extraction and use of  insulin,

and by

Werner and Bell (Dublin 1922)   on the first synthesis of dimethylguanidine- metformin.

DIABETES AND CANCER INCIDENCE:

*The Finnish ATBC study 2006 showed that the worst obesity and metabolic syndrome associated with 40% increase in bowel especially rectal cancer.

*In older obese women in Italy 1999, type 2 diabetes tripled the incidence of endometrial cancer.

*In a 10year study in Jena, Germany (2005), insulin-treated diabetics  showed a 10 fold increase in cancer (mostly rectum and colon)  compared to the control population.

*In a study of pancreas cancer in Italy 2004, pancreas cancer was three times more common in those with type 2 DM than in non-diabetics.

*We have previously reviewed the evidence that lowering lipidemia – hypolipidemia– with statins may increase cancer risk, without reducing insulin resistance or diabetes risk.

A new trial from the Univ Connecticut last month , and two new reviews last week- from the European Institute of Oncology and the University California,  strengthen the case that meformin is a crucial cancer preventive and therapy, that by promoting AMPK at the cellular level, it switches off cancer cell proliferation ie immortality, while promoting anti-aging in all healthy tissues.

METHODS: Pubmed and Google search for English  abstracts under “metformin AND CANCER”

RESULTS:

There are now at least 12  studies and trials of metformin and cancer available on Pubmed and through the internet;

too disparate  to do a metanalysis, but certainly a review offering nothing but good news:

Metformin has been reported in studies to produce less cancers and cancer-related deaths than occur without it ie with insulin or sulphonylureas or without any antidiabetic drugs:

metformin and cancers in human :

* 29% fewer cancer deaths (non significant) in diabetics after mean 13.6yrs –UKPDS 1998;

* reverse endometrial hyperplasia in a woman-  2003 Mayo clinic ;

*perhaps 21% fewer cancers in diabetics on metformin Tayside UK 2005

*25% less cancers in human diabetics than those treated with other antidiabetics  Canada 2006;
* Increases Pathologic Complete Response Rates in Breast Cancer Patients With Diabetes Univ Texas 2008.

*metformin benefit on cancer in human cancer cell cultures:

Prostate cancer in vitro  France 2008

lung cancer in vitro Univ Arizona 2005;

breast cancer in vitro -McGill, Canada 2006, and Univ Connecticut 2009;

colon cancer in vitro Pennsylvania 2007;

ovarian cancer McGill 2008;

and in hamsters: pancreas cancer Nebraska 2001;

and in mice lung cancer McGill 2008 ..

YET USA Industry and regulators – owing to obvious commercial vested interests- take the indefensible stance that eg human estriol is an unregistered new drug that must be proven in trials. It is said that no new drug can be registered there before an average of $600million has been spent on research and trials. So no sane for-profit company is going to fund trials on an unpatentible natural molecule – especially a sex hormone that has evolved in humans for millions of years , without a single reported case of natural or use-related adversity.

The same goes for metformin- a natural plant derivative first isolated 87 years ago, the only drug ever tested in a 20year RCT- and proven in numerous trials and controlled studies to have zero serious adverse effects, and proven to be a panacea- the only drug effective against virtually every major chronic degenerative disease of aging.

Yet threatening regulatory concern is hypocritically expressed – without the slightest evidence against it – when metformin  is used as the only evidence-based drug to prevent and reverse the epidemic complications of overweight BEFORE obesity, PCOS, hypertension, arthritis, diabetes, CVD, stroke, visual / renal impairment, neuropathy, or cancer present.

CONCLUSION:

It is well shown in studies that waiting for obesity let alone diabetes increases major disease let alone premature death by 2 to 5 fold; and that used in prevention it reduces the incidence of new diabetes by 30% to 90% in a dose-dependent fashion up to reasonable dose tolerance; and in type 2 diabetes halves the incidence of premature death.

So since  metformin is  associated with reduction of even cancer, it should (except in terminal or wasted non-diabetic patients, or temporarily in unstable renal or respiratory-metabolic function)  be added cautiously and titrated up to moderate dose short of intolerance in any patient presenting at any age after 12yrs if not younger with rising overweight ie BMI much > 25kg/sqm or waist girth much >80cm, unresponsive to diet and lifestyle attempts

Dedicated  to    (mal)nutrition- metabolic syndrome – PCOS – diabetes – cancer and metformin  sufferers, and researchers:  Werner and Bell (Dublin);   Sirs Harold  Himsworth and   Stanley Davidson (UK);  Professors  Jack Brock, Stewart Truswell and WPU Jackson at University of Cape Town UCT; Frank Maudsley Parsons (Univ Leeds); Rick Turner and Rury Holman(UKPDS); Gilbert Forbes, Tim Lohman, Gerald  Reaven, Fred Naftolin, Charles Glueck (USA); and the DPPRG trialists on all continents.

DEATH OF A YOUTH BY ACNE TREATMENT SYMBOLIZES THE RUTHLESS ALLOPATHIC DESIGNER MEDICAL PARADIGM.

This isolated  case in UK –  a tragedy of  anaphylactic death from a tetracycline  for zits-   is the tip of the mountain that thinking western society refuses to confront.

As London University philosopher AC Grayling says in his short but illuminating essay on Kuhn and Popper in The Form of Things:

  • Austrian-refugee  British philosopher-economist Karl Popper (b1902), who in Grayling’s view preached the crucial “spirit of scientific inquiry, that science proceeds by conjecture and refutation, subjecting ideas to rigorous testing to try to prove them false. If they survive, they are not guaranteed to be true, but they can be used as long as they remain unrefuted.”
  • American physicist Thomas Kuhn (b1922) made famous  the term ‘paradigm shift’,  and the now-dominant cynical  pragmatism that has led the world to the war-torn economic anarchy we now wallow in: “crucially, old and new paradigms are ‘incommensurable’, so when difficulties accumulate making the existing paradigm of enquiry unsustainable, it is arbitrarily replaced by a new ‘normal science’, even if the new is not better”.            This is the havoc caused by two millennia of the power-mad Christian  (and it’s offspring  Islamic) hierarchies  (not their pious thinking  followers of  their prophets and Books) , that led to the shift from pagan GrekoRoman oligarchy BC  to unprovable mind-controlling religion- based society AD, back to  to the equally amoral genocidal oligarchy   ( Christian, Islamic, Asian) societies of the past 1500 years.                              And finally  the young  Milton Friedman(b 1912)   and Henry Kissinger(b1923) during the post-WW2 years developed  “free market” economics that they spread from the Nixon administration onwards, recruiting Ronald Reagan,  George  Bush sen.(b1924) and jun.(b1946) , Dick Cheyney(b1941), Donald Rumsfeld (b1932)   and Paul Wolfowitz (b1943) (even Bill Clinton b1946)  post Vietnam in abolition of trade barriers,  minimum wages and rights for the poor workers, disaster capitalism, two foreign wars on the go at any time to boost the USA economy.    And the same Bush quartet, with Henry Kissinger, have seen to the pursuance of that policy- with a vengeance- until last month.                    And not least, the escalating FDA’s War against Humanity, in the interests of the American Disease Industry.  As Grayling writes, the enforcement of convenience  science- and pseudoscience like the statin and Women’  Health Initiative trials –   that suit and confirm the  legitimacy  of the dominant social institutions.
  • Grayling thus reasons that Kuhn’s American (pseudo) science viewpoint has been embraced by postmodernists, relativists, capitalists, precisely because it is empiric and opportunistic; whereas  old-world Eurocentric  Popper’s  evidence-based doctrine  (like Ivan Illich, Fritz Schumaker and Linus Pauling)  brings us closer to  the enduring truth of things. (I happened to hear Schumaker speak on Small is Beautiful in Yorkshire in 1974, and happened to be in London in 1994 when two of the ethical icons of the 20th century – Popper and Pauling –  died in righteous old age).

We know only too well  the history of oppressive ruthless  medical terrorism in the Western world the past two centuries, from

  • forced female institutionalization, castration and clitoridectomy by eminent Victorian physicians,  through to mass criminal medical negligence if not murder  in  our lifetime in “European”- descended  countries-  to
  • Australian and Nazi sterilization policies
  • to the infamous USA  Tuskegee syphilis experiment that was allowed to run until the 1970s,  to
  • the already scientifically unjustified disastrous 1950 Chicago Lying-in Hospital trial of DES diethylstilbestrol (whose ongoing manufacture was still allowed to continue to blight women for another 20years)  to
  • the blockade in the USA for decades of already well-proven evidence-based  lifesaving lithium and metformin,
  • to the ongoing promotion and protection  till today of oral xenohormones- equine estrogen and synthetic progestins by regulators despite evidence that they are as good and safe as the parenteral human hormones that have been proven by evolution and now use for sixty years,  to
  • the increasing move by the Disease Industry and it’s Regulators to suppress or make prescription-only (after far more mandatory testing than most patented drugs went through) the natural and best unscheduled over-the-counter drugs ( the nutritional supplement and therefore unpatentable vitamins, minerals, and biologicals including eg coQ10, carnitine, carnitine, chondroglucosamine, and therapeutic herbs, and human hormone creams)-
  • while making statins mandatory for all, available over-the-counter,  chronic  designer for-profit inventions whose safety was never tested in even medium-term (5 year) RCTs before release, and whose use has never been justified for mild to moderate hypercholesterolemia considering their poor longterm compliance due to terrible incidence of serious insidious adverse effects, and the obvious fact that (unlike eg the 50year proven metformin and other natural supplements), they do nothing for the other half of major chronic morbidity and premature mortality- the non-cardiovascular plagues like obesity, diabetes, arthritis, osteoporosis, cancer.

To return to a single unnecessary  death after treatment of acne: the fact that  the drug  was a different generic minocycline to that prescribed  is a smokescreen that must  not distract from the core problem of the failure of western culture and medicine:

a  sick (TV- media-dominated) poorly educated  society that puts cosmetic perfection  at the pinnacle: and

a for-profit  disease-industry-dominated allopathic culture that teaches and encourages synthetic modern designer drugs and  technology to be used  as  first, not last resort.

Why should a  young man with what was apparently simple acne-  spots, zits (nowhere do the media reports use the words “gross” or “globular” or “deforming” or “scarring” to describe his condition) – be prescribed an antibiotic let alone Roaccutane ?

Were all the safer remedies tried,  from diet change to de-stress to reassurance to homeopathy to safe oral and topical nutritionals?

Since when is simple acne an indication for an antibiotic let alone a  systemic antibiotic? when

1. there is lethal mushrooming of antibiotic resistance and

2. deadly complications can follow most  modern designer drugs, whether from the drug itself or the additives necessary to make pills and lotions.

The same question applies to most modern drugs, especially for chronic non-life-threatening conditions.

Unlike our natural armamentarium of the best drugs available- wholesome food topped up with long-proven vigorous safe vitamins, minerals, and biologicals- fish (oil)-  and plant- derived;

modern designer  drugs rarely address the underlying cause– in this case as always, multi-factorial including the degraded food chain and atmosphere,  competition and worsening global  bad news  rammed down our throats every waking minute by the media, thus stress & nutritional/pollution immuno-incompetence and hormone domination.

It’s the same question that must be considered in every consultation:  why- except in the rare  severe refractory case-  prescribe  any major procedure / investigation or modern designer drugs- antibiotic, statins, nonsteroidal anti-inflammatories, bisphosphonates, xenohormones, psychotropes, antihypertensives until the old and proven have been tried?

When no modern designer drug (from eg the above $trillion- a- year army)  has been or will be tested long-term ie for beyond 2 years before it’s launch, or has a record of at least 20years of good and safe experience behind it eg

*in all cases including acne, osteoporosis, mild infection (which is often indistinguishable from transient allergy)   the listed supplements plus sensible heeded diet-lifestyle ; plus

* low-dose reserpine plus low-dose amiloretic for hypertension (>40years experience and trial);

* metformin (>50 years experience in use, 20year RCT) for overweight, lipidemia, PCOS, metabolic syndrome, type 2 diabetes, cancer;

* human hormones by the most  appropriate route for hormone deficiency states.

Hence for this death  it is the Regulator, the medical schools, the national health and legal system  that should go on trial- not the drug or the too- obedient doctor who blindly followed the rules.

I nearly succumbed twice  from rapid paroxysmal atrial fibrillation  recently:  the first time  under general anaesthetic for a dental extraction. But the extraction was necessary because of a broken, dead, unsavable tooth, that my dentist could not shift in his rooms; so I was in a hospital theatre with a maxillofacial surgeon, a skilled anaesthetist, on  a monitor; and an intensivist close by.   Now, after subsequent severe acute heart failure from worsening  decades-old lone atrial fibrillation that was no longer controlled by fish oil, I am in mostly sinus rhythm on digoxin, verapamil, furosamide, spironolactone- and 4 grams fish oil a day since the prescription drugs do not prevent my atrial fibrillation without the fish oil.  So I delay the offer of nodal ablation since there is no guarantee that this will not leave me worse off.

Thirty years ago I was blinded for a few days by severe allergy from chloramphenicol eyedrops prescribed by a consultant ophthalmologist- for what started as a lawn- cutting grass-induced conjunctivitis…

It begs the point of JUSTIFICATION to argue that serious reaction is rare, and death even rarer, from oral tetracycline, or  eyedrops, or NSAID, or ACEI or statin or bisphosphonate or psychotrope, when safe natural remedies should have been exhausted first, and step-up to riskier or modern drugs justified..

So it is   the NHS that should be indicted, not the drug. It is the well-paid NHS politicians, Regulators  and top management  in their own personal capacity , not the taxpayer, who should pay the bereaved family compensation for negligent death.

NDB.

STATINS-FOR-ALL IS BAD PHYSIOLOGY – WE NEED CHOLESTEROL

Golomb and Evans’ focus in their new review of adverse effects of statins omits the more important half of the equation: PHYSIOLOGY.

We, our metabolism need cholesterol for optimal metabolism. Blocking it’s production is wrong in the great majority, in whom (as in type 2 DM) the primary problem is insulin RESISTANCE. Unlike pure sugar, cholesterol per se is not toxic.

We know well that lowering blood sugar in such patients- with eg sulphonylureas, glitazones or insulin- or lowering thrombosis with warfarin- more often does the opposite of reducing mortality and multisystem diseases of aging.

Unlike eg toxins like heavy metals, just eliminating simple sugars or salt from the diet doesnt lower diabetes/ hypertension much.    Hence metformin in combination with it’s many natural fellow insuln sensitizers- antioxidant- NO-boosters ( vitamins-minerals and biologicals including fish oil, coQ10, arginine, appropriate non-oral human sex hormones, herbs) – is the correct  life-extending approach;

except in the rare severe resistant hypercholesterolemia where adding a lowdose statin can only improve prognosis.

DIET ALONE- WHATEVER THE CONTENT- DOES NOT SUSTAIN EVEN 4% WEIGHT LOSS- ONLY METFORMIN DOES.

Today’s NEJM major diet study from Harvard University confirms:

it doesn’t matter what the weight-loss diet composition is so long as calories are down:

Each participant’s diet prescription represented a 750kcal/day deficit; with 90mins moderate exercise a week. .

mean previous baseline intake was 2000 kcals/day- 18% protein (ie +- 90gm) , 37% fat ie +-70gm) , 45% carbs (ie +-200gm). No initial trial diet had less than 1200 kcal/d.

RESULT: weight loss is +- 6kg by 6months  but only +- 4kg (4.3%)  by 2yrs , with waist loss +- 4cm – whether FAT intake was 20 or 40%, PROTEIN 15 or 25%, CARBS 65 or 35%.

The bad news remains that, despite participants attending regular motivation, on average weight rose steadily after more than 6 months on diet.

This confirms what is constantly urged in this column, that since titrated metformin consistently maintains about 6% better weight reduction than sustainable diet alone- without any serious adverse risks whatsoever, just +-50% reduction in diabetes and all major chronic degenerative diseases  –  metformin to tolerance should always be added to prudent diet  where overweight needs to be reversed or at least stopped.

It is folly to delay metformin  till the features of PCOS or metabolic syndrome, let alone diabetes, cancer, CVD , damaged joints and minds appear. It is criminal to allow average  patients of any age to become increasingly overweight without adding the safest chronic drug ever discovered (metformin* 1922), the only drug that has been proven 100% safe from  serious adverse effects n sensible use in controlled & followup  trials of up to 30years- and in major prevention trials  lower new diabetes by up to 90%.

*Of course metformin is not the only effective agent- it is merely the only registered prescription drug that safely reverses both appetite overeating, insulin resistance and all the complications.  And many doctors and administrators perversely, dangerously  will not read the evidence, they insist that it may not be prescribed just for overweight- they demand that the patient must first take ill..   A broad combination of natural alternatives that this column regularly lists  can do better- but has to be both sourced and paid for.

THE STATIN BUBBLE BURSTS:STATINS CAUSE MUSCLE SYMPTOMS IN 50% MORE THAN NONUSERS IN PRIMARY CARE – WITHOUT REDUCING NEW DIABETES!

A new study from University of Tübingen shows that in 1000 consecutive patients in primary GP care, the incidence of muscular symptoms was FIFTY PERCENT  higher in those on lipid-lowering drugs LLD – statins-  than those not.

There can be few other nations  as methodical and meticulous as Germany, so it is unlikely that their  LLD patients were being unnecessarily or excessively treated.

As this column regularly points out,  statins do not address the basic pathogenesis of common lipidemia  ie  overeating/overweight/ insulin resistance. Hence statins  in general reduce even cardiovascular disease CVD  no more than 40%, and overweight, diabetes and  non-CVD not at all.

So  statins inflame muscle even in moderate dose.  Thus is it any  surprise that despite their claimed beneficial effect on circulation and CRP, they have no benefit in reducing heart failure in recent major trials?  whereas in a rat study metformin has just been confirmed to halve heart failure. As a team from Univ Dundee UK wrote last year,  “there is increasing evidence to suggest that chronic heart failure (CHF) is an insulin resistant (IR) state and that the degree of IR correlates with the severity and mortality of CHF.. there is now evidence that metformin may not only be safe but could potentially be useful in the setting of CHF.”

So we must always ask:  why (except to profit the manufacturers) use statins except in severe refractory lipidemia?  In a recent meta-analysis from Albert Einstein College  and Cleveland Clinic, once again  there is no evidence that statins reduce the incidence of new diabetes.

whereas  metformin halves new diabetes , reduces overweight in the major preventive RCTs, and in diabetics type 2  virtually halves all chronic major degenerative diseases of aging, and premature mortality.

METFORMIN RELIEVES MENOPAUSE SYMPTOMS- hot flashes, fatigue, sweating – let alone HEART FAILURE

A new report from University of Louiseville describes 3 patients with resistant  menopausal syndrome- hot flashes, fatigue and sweating- referred for endocrine workup; who proved to have hyperinsulinemia with normal glucose tolerance, and recovered on metformin 1gm/day.

This bears out

  • that the  average natural fat gain around the menopause- which is aggravated by oral estrogen-progestin(HT)- is perhaps more amenable to the co-hormone metformin (or numerous natural insulin-sensitizing equivalents) than  to generally adverse risky oral HT;
  • and  the weight gain and insulin resistance are best reduced by metformin, which reduces the high risk of all the chronic degenerative diseases of aging that accelerate around menopause. If sex hormone replacement is still required, it is best used physiologically as non-oral balanced appropriate hormones based on restoration of average youthful blood levels eg with testosterone, estradiol and progesterone.

One must just remember that

  • sensitivity to metformin varies greatly genetically  as well as by size, so dose should always be started low eg ~125mg/day and titrated up over a few days to establish tolerance;  (and the dose backtitrated if necessary to avoid symptoms eg nausea, diarrhoea. Metformin on it’s own with sensible diet never produces hypoglycemia;.
  • Demonstration of insulin resistance let alone a raised blood glucose is often the extra motivation needed to persuade patients to stop using sugar and sugared foods/drinks, let alone  cook fat-free .
  • and that middle-aged patients who present  should routinely have a fasting, and fed (at least eg 90mins after a can of Coke) blood glucose and insulin level, if not a full glucose-insulin tolerance test.

Another new study from Canada shows that even in patients around 77 years of age with diabetes and heart-failure, many are already being treated with metformin- a mean of about 1.7gm/day-  indicating that there, there  is no uncertainty about it’s safety and benefits under supervision.  This is confirmed by a simultaneous publication from Albert Einstein College (Bronx) in which the use of lowdose metformin after experimental heartfailure in mice improves survival by 47%, through activation of AMPK- just as metformin improves thrombolysis, and  energy uptake in all muscle (let alone improving bloodflow by lowering fibrinogen, inflammation, CRP).

Hence starting metformin preventively in the overweight / lipidemic – even before obesity, hypertension, lipidemia, depression, cancer, diabetes, vascular disease  and heart failure supervene-  can only be even better and safer.

META-ANALYSIS: METFORMIN – THE ONLY DRUG WHICH SAFELY AND LIFESAVINGLY LOWERS CRP, OVERWEIGHT AND RELATED INFLAMMATION.

Medline was started in 1966  but has been expanded to record journal papers back to 1950. There are already 768 RCT metformin references  listed on Medline since 1969; and 323 on metformin double blind RCTs (compare lithium- since the first in 1968,  respectively 611 and 335 reports).  Obviously many of these  RCTs refer to it simply as background or previous or exclusion therapy or  alternatives.  In the 50 latest  of the 323,   metformin was distinctly involved in 42% as one of the trial  arms; in the 50  earliest, 52% involved diabetes as one of the primary trial arms.

Thus  there are perhaps 150 published double blind RCTs of metformin  itself, (which after lithium- (used from about 1850)  must  thus be  the longest   (over 40years)  and still  regularly  used and tested single chronic “drugs”. Reserpine (isolated in 1952 from a centuries-old medicinal plant) dating from the first report in 1966 is still like metformin and lithium the gold standard in it’s field of hypertension,  but with only 74 and 47 reports respectively reflecting the concerted collusion of drug regulators and the drug industry to try to suppress it by no longer using it as a gold standard for comparison. All three are uniquely safe and effective in their fields provided doses are appropriately tailored. Since  these old drugs  have  been in clinical use already for > 50years,   there may be more  RCTs than those listed.

Paracetamol has been in use almost the longest of any synthetic drug (from 1886), but ( unlike metformin, lithium and reserpine ) is  contraindicated   for long term chronic daily prevention.

But the centuries-old appetite-overweight–diabetes-reducing plant galega officinalis finally yielded up it’s unique antihyperglycemic guanide secret when  dimethylguanidine- metformin was isolated 86 years ago in Dublin, Ireland  by Werner and Best,  the same year that insulin was isolated  in Canada under the leadership of another visionary Celtic British Isles physiologist,  John Macleod from Aberdeen.

If Banting and Macleod deserved the 1923 Nobel prize for insulin for DM1,  more so did Werner and Bell for isolating metformin for DM2 when almost 95% of diabetics are now type 2.  But hindsight is great.  DM2 was only recognized a decade after insulin and metformin’s extraction  (Himsworth, the Lancet 1936),  like gout a relatively rare disease of lazy overindulgence  for obvious reasons   until the fast foods and prosperity – expanding waistlines from  the 1950.  So there was no impetus to develop metformin commercially in it’s first 30 years,  in obvious contrast to the need for insulin for  the scourge of wasting juvenile diabetes mellitus type 1 DM1 in millions of young sufferers already in the 1920s.

Werner and Bell need to be honoured   as isolating by far  the most important chronic drug of our time  for the epidemic chronic degenerative diseases of aging in the increasingly overweight since the 1950s, (and especially with AIDs and ARVs  increasing metabolic syndrome). It is a  prohormone that in the overweight improves the  function of the vital hormone insulin,  if started preventively before diabetes and obesity develop, largely preventing  obesity and  metabolic syndrome MBS, and thus  more than  halves the incidence and mortality of diabetes and it’s fellow scourges: vascular disease, cancer, infection, arthritis etc.  It has also been shown to be a prohormone in lowering TSH without affecting thyroid hormone levels, thus further reducing the tendency to obesity- related high SHBG in women with PCOS. Metformin, like lithium and reserpine,  is thus  bad news indeed for the Disease and Undertaking industries, to be blocked and replaced by new designer drugs  at any cost.

Insulin by contrast cannot be swallowed, and works well  and extends life long term only in DM1.  The longest (20year – mean 13.6yrs – from 1978 to 1998) drug trial ever – on metformin and sulphonylureas,  the UKPDS,  has just had  the 10year follow-on  published.But  Chakrabarti and Fearnley in UK already in 1965 described the fibrinolytic effect of metformin in coronary artery disease- and  the USA chose to obstruct  obstruct metformin  till 1995.

So while DM1 was conquered in Canada, it was  in the British Isles that DM2 was first delineated (Himsworth 1936), and metformin isolated(1922)  and  established for coronary artery disease (1965) and  and uniquely validated  for DM2 and lipidemia and all-cause mortality  protection (1978-2008 – Holman ea).

But  the trials confirming metformin’s unique role in improving function and outcomes in PCOS and infertility(Glueck ea), and in reversing peripubertal obesity- growth delay- DM2 (Freemark ea) ,  and the delineation of PCOS (Stein & Levinthal, Chicago 1935)  were mostly done in USA;

and the landmark Diabetes Prevention Program  DPP trials in  primary prevention in the overweight,  showing that metformin  can more than halve  the incidence of new diabetes,  were carried out the past  decade  in China (Wenying ea 2001), USA (Knowler ea 2002)  and  India (Ramachandran 2006)  if built up slowly from low dose (eg 125mg/day up to tolerance – a mean of about 2.7gm/d in caucasoids.

METANALYSIS of metformin effect on CRP C reactive protein: if one counts just abstracts and full papers on metformin and CRP reported on Medline and the internet, a study this month from Univ College London is at least the 14th prospective study. These  studies-  from   USA(4), UK(2),  Saudi ArabiaFinland,   GreeceBosniaItalyBrazil, Mexico and   Israel, looked at metformin’s effect on inflammation – CRP,   between 2002-  and now -the paper by Chu,  Reaven ea at Univ Calif San Diego;   in +- 4000 subjects (20 to 3234); 6 studies with diabetes mellitus DM2; 5 studies with PCOS polycystic ovary syndrome, and 3 in metabolic syndrome MBS. These papers – including 4 RCTs-  exclude those which looked futilely at burnt-out – advanced- resistant DM2 ie in those who refused to comply and reduce obesity.

This metanalysis confirms that metformin in effective dose (they tested between 850-2000mg/day for 1 to 12 months)- not even   titrated to tolerance –  reduces  inflammation (reactive oxygen species,  VLDL ,  raised white cell count, fibrinogen and CReactive Protein CRP); which partly explains why it is the only drug ever discovered which lowers both appetite, overweight, abdominal girth, hypertension,  leptin, insulin resistance; hot flashes (due to everyday insulin resistance); cancer,  hepatitis, fatty liver, blindness,  kidney failure, neuropathy, gout, infectivity, CVD, stroke, arrhythmia, heart-attack, heart failure, dementia; and halves both CVD and non-CVD mortality and new diabetes;  while promoting nitric oxide, HDL, fertility, successful pregnancy, normal infants and childhood growth.

It is the only drug ever tested in an RCT lasting 20years; and the only drug that in numerous RCTs has never shown a serious unpredictable adverse effect let alone related fatality.

But ignoring overweight, hypertension and PCOS, waiting till obesity let alone diabetes mellitus DM2 develops before starting metformin is negligence, since DM2  already increases risk of the many complications and death fourfold; and waiting till DM2 is severe before reversing weight gain with metformin, now   requiring hypoglycemic drugs, is a criminal, terrible risk of heart, brain, kidney, limb and eye failure and premature death.

Titrated from low starter dose to tolerance – ideally with blood metformin level monitoring like many other chronic drugs – with sensible diet and without hypoglycemic drugs- metformin has no serious adverse effects ie risks. Tendency to diarrhoea and raised homocysteine can easily be prevented by  both sensible dose titration and some supplement of calcium carbonate, folic acid B12 and B6- which should anyway be taken regularly as part of multisupplement for prevention of the whole group of interrelated chronic major degenerative diseases of aging .

Since it is eliminated exclusively by the kidneys, the absolute contraindications to metformin are temporary and obvious on simple observation – oligoanuria and/or acidosis (unexplained rapid breathing/ hyperventilation); and it should be stopped for a few days around xray contrast media injections..   As with any other drug, it should be briefly reduced to low dose (and if no rapid improvement, stopped) and the doctor consulted if new symptoms eg nausea, bloating, abdominal pain, faintness, confusion, unstable urinary output, rapid breathing  or diarrhoea develop; and the dose re-titrated more cautiously to tolerance.

Strangely, a Statement by the American Heart Association and the NHLBI on Diagnosis and Therapy of the Metabolic Syndrome as recently as 2005  negligently failed to mention metformin as the only agent that safely and effectively lowers all inflammatory markers and risks – despite three crucial  abstracts/papers already Medline-listed by 2003.

But given the universal availability of Medline, clinicians  are bound first by their primary duty  to practice evidence-based medicine that matters to patients. They cannot hide behind the ignorance, regulations, omissions and smokescreens of Big Pharma, regulators- bureaucrats;  and especially  academics who are heavily influenced by  conflicts of  vested interests.

$Billions are  spent futilely  by Big Pharma  to invent and dishonestly register and  market risky raincheck  designer chronic  drugs that attempt without success to give  the crucial healthspan-prolonging multisystemic benefits of metformin (and fish oil, and appropriate vigorous supplements- vitamins, minerals and human biologicals like CoQ10 and  non-oral sexhormone replacement), – including sulphonylureas, glitazones, gliptins, statins, fibrates, oral xenohormones, appetite suppressants NSAIDS and antithrombotics, ACEIs and ARBs.

Statins for example – which now gross perhaps $20billion a year in sales-  have just  been shown in a UK  1991-2006 analysis (compared to controls) to increase   myopathy/myalgia by 10fold at 3 months, 20fold by 6 months and 27-fold at 1 year; with 10year incidence of about 0.7%.  This compares with the 10year risk of hospitalized  rhabdomyolysis in USA patients on modern statins of  0,044%.

But a 2007 analysis from Boston of the 23 large statin RCTs in 300 000 patient years  showed inverse relation between LDL lowering and cancer – and in the  recent Hong Kong study (Yang, Chan ea 2008), the cancer and death  rates rose progressively when LDLC levels fell   below a mean of 3.28mmol/L, while in the 2008 Baltimore statin meta-analysis in people from 60yrs upwards, cancer increased by 6% on statin.

Few of these   wannabe new drugs are subjected to even 2 years of RCT, let alone the 20year RCT of metformin, before being launched on the innocent casualties, the public,  by Big Pharma’s  for-profit-at-any-cost War against Humanity.

Everything in life is potentially dangerous in excess, from food to love to oxygen to water; but common sense- experience- soon teaches safe doses. There is a criminal, hypocritical   regulatory obsession  that insists that metformin must be reserved only for PCOS and DM2 but is too dangerous to prescribe to prevent increasing overweight and disease – when it is the most-proven and safest modern drug for prevention of overweight and obesity that fuels the chronic major degenerative diseases.

A recent innovative study from  the Hatter CVD Institute at University College London shows that metformin almost halves myocardial infarction size in both normal and diabetic rats. So why is it’s use so restricted, when cigarettes, the statins and NSAIDs- with multiple serious adverse effects- are allowed over-the-counter?

Metformin seems to be the only drug which addresses all organ systems that appear to be involved in the primary pathophysiology of DM2 -metabolic defects in liver and in peripheral target tissues, such as fat and muscle and pancreatic β cells.

One need look no further than the overwhelming profit motive   that drives  the $trillion disease  industry to prefer diseases that pay to effective prevention which would more than halve the need for common drugs and acute care,   that avoids banning  the sale of eg cigarettes  and   sugar, and avoids mandatory immediate long jail term and confiscation both  of driver’s license and vehicle  and gun license for drunken driving especially with a weapon.

This paradox is especially obvious in the most violent warmongering “civilized” country in the world this decade under the Bush Gang- the USA – that confiscates even houses of those who grow proven medicinal cannabis for personal use, when cannabis has been long proven to have perhaps one thousandth of the toxicity of sugar or  cigaretes,  and a fraction of the risks of alcohol overuse .

This is the self-styled 1st-world  country that leads the world – especially   it’s parent Europe-  in trying to suppress  natural proven nutritional supplements – eg the (pro)hormones  metformin and non-oral human estrogen, testosterone and progesterone, which  work against  the causes  and mortality of common degenerative disease.

They do  this so as to favour their own costly but risky and inferior  chronic designer drugs and acute disease industry that rarely help  resolve the chronic major aging diseases. .  As usual, they promote diseases  that pay,  while preaching the opposite.